Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells
The porcine reproductive and respiratory syndrome virus (PRRSV), especially the highly pathogenic strains, can cause serious acute lung injury (ALI), characterized by extensive hemorrhage, inflammatory cells and serous fluid infiltration in the lung vascular system. Meanwhile, the pulmonary microvas...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/14/3/452 |
| _version_ | 1797441118538825728 |
|---|---|
| author | Weifeng Sun Weixin Wu Nan Jiang Xinna Ge Yongning Zhang Jun Han Xin Guo Lei Zhou Hanchun Yang |
| author_facet | Weifeng Sun Weixin Wu Nan Jiang Xinna Ge Yongning Zhang Jun Han Xin Guo Lei Zhou Hanchun Yang |
| author_sort | Weifeng Sun |
| collection | DOAJ |
| description | The porcine reproductive and respiratory syndrome virus (PRRSV), especially the highly pathogenic strains, can cause serious acute lung injury (ALI), characterized by extensive hemorrhage, inflammatory cells and serous fluid infiltration in the lung vascular system. Meanwhile, the pulmonary microvascular endothelial cells (PMVECs) are essential for forming the air–blood barrier and keeping the water–salt balance to prevent leakage of circulating nutrients, solutes, and fluid into the underlying tissues. As well, they tightly regulate the influx of immune cells. To determine the possible relationship between the PMVECs’ function changes and lung vascular permeability during PRRSV infection, the PMVECs were co-cultured with HP-PRRSV-inoculated primary pulmonary alveolar macrophages (PAMs) in transwell model, and then the RNA sequencing (RNA-seq) and comprehensive bioinformatics analysis were carried out to characterize the dynamic transcriptome landscapes of PMVECs. In total, 16,489 annotated genes were identified, with 275 upregulated and 270 downregulated differentially expressed genes (DEGs) were characterized at both 18 and 24 h post PRRSV inoculation. The GO terms and KEGG pathways analysis indicated that the immune response, metabolic pathways, cell death, cytokine–cytokine receptor interaction, viral responses, and apoptotic process are significantly regulated upon co-culture with PRRSV-infected PAMs. Moreover, according to the TERR and dextran flux assay results, dysregulation of TJ proteins, including CLDN1, CLDN4, CLDN8, and OCLN, is further confirmed to correlate with the increased permeability of PMVECs. These transcriptome profiles and DEGs will provide valuable clues for further exploring the roles of PMVECs in PRRSV-induced ALI in the future. |
| first_indexed | 2024-03-09T12:19:23Z |
| format | Article |
| id | doaj.art-f1d1c2499a5e454fa4e5f14f363d9277 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T12:19:23Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-f1d1c2499a5e454fa4e5f14f363d92772023-11-30T22:43:39ZengMDPI AGViruses1999-49152022-02-0114345210.3390/v14030452Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial CellsWeifeng Sun0Weixin Wu1Nan Jiang2Xinna Ge3Yongning Zhang4Jun Han5Xin Guo6Lei Zhou7Hanchun Yang8Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaKey Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaKey Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaKey Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaKey Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaKey Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaKey Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaKey Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaKey Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaThe porcine reproductive and respiratory syndrome virus (PRRSV), especially the highly pathogenic strains, can cause serious acute lung injury (ALI), characterized by extensive hemorrhage, inflammatory cells and serous fluid infiltration in the lung vascular system. Meanwhile, the pulmonary microvascular endothelial cells (PMVECs) are essential for forming the air–blood barrier and keeping the water–salt balance to prevent leakage of circulating nutrients, solutes, and fluid into the underlying tissues. As well, they tightly regulate the influx of immune cells. To determine the possible relationship between the PMVECs’ function changes and lung vascular permeability during PRRSV infection, the PMVECs were co-cultured with HP-PRRSV-inoculated primary pulmonary alveolar macrophages (PAMs) in transwell model, and then the RNA sequencing (RNA-seq) and comprehensive bioinformatics analysis were carried out to characterize the dynamic transcriptome landscapes of PMVECs. In total, 16,489 annotated genes were identified, with 275 upregulated and 270 downregulated differentially expressed genes (DEGs) were characterized at both 18 and 24 h post PRRSV inoculation. The GO terms and KEGG pathways analysis indicated that the immune response, metabolic pathways, cell death, cytokine–cytokine receptor interaction, viral responses, and apoptotic process are significantly regulated upon co-culture with PRRSV-infected PAMs. Moreover, according to the TERR and dextran flux assay results, dysregulation of TJ proteins, including CLDN1, CLDN4, CLDN8, and OCLN, is further confirmed to correlate with the increased permeability of PMVECs. These transcriptome profiles and DEGs will provide valuable clues for further exploring the roles of PMVECs in PRRSV-induced ALI in the future.https://www.mdpi.com/1999-4915/14/3/452porcine reproductive and respiratory syndrome virus (PRRSV)pulmonary microvascular endothelial cells (PMVECs)transcriptome analysistranswell co-culturescytokinestight junctions (TJs) |
| spellingShingle | Weifeng Sun Weixin Wu Nan Jiang Xinna Ge Yongning Zhang Jun Han Xin Guo Lei Zhou Hanchun Yang Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells Viruses porcine reproductive and respiratory syndrome virus (PRRSV) pulmonary microvascular endothelial cells (PMVECs) transcriptome analysis transwell co-cultures cytokines tight junctions (TJs) |
| title | Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells |
| title_full | Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells |
| title_fullStr | Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells |
| title_full_unstemmed | Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells |
| title_short | Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells |
| title_sort | highly pathogenic prrsv infected alveolar macrophages impair the function of pulmonary microvascular endothelial cells |
| topic | porcine reproductive and respiratory syndrome virus (PRRSV) pulmonary microvascular endothelial cells (PMVECs) transcriptome analysis transwell co-cultures cytokines tight junctions (TJs) |
| url | https://www.mdpi.com/1999-4915/14/3/452 |
| work_keys_str_mv | AT weifengsun highlypathogenicprrsvinfectedalveolarmacrophagesimpairthefunctionofpulmonarymicrovascularendothelialcells AT weixinwu highlypathogenicprrsvinfectedalveolarmacrophagesimpairthefunctionofpulmonarymicrovascularendothelialcells AT nanjiang highlypathogenicprrsvinfectedalveolarmacrophagesimpairthefunctionofpulmonarymicrovascularendothelialcells AT xinnage highlypathogenicprrsvinfectedalveolarmacrophagesimpairthefunctionofpulmonarymicrovascularendothelialcells AT yongningzhang highlypathogenicprrsvinfectedalveolarmacrophagesimpairthefunctionofpulmonarymicrovascularendothelialcells AT junhan highlypathogenicprrsvinfectedalveolarmacrophagesimpairthefunctionofpulmonarymicrovascularendothelialcells AT xinguo highlypathogenicprrsvinfectedalveolarmacrophagesimpairthefunctionofpulmonarymicrovascularendothelialcells AT leizhou highlypathogenicprrsvinfectedalveolarmacrophagesimpairthefunctionofpulmonarymicrovascularendothelialcells AT hanchunyang highlypathogenicprrsvinfectedalveolarmacrophagesimpairthefunctionofpulmonarymicrovascularendothelialcells |